Thesis (M.D.)--Boston University

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Cancer, the second most common cause of death in the United States, is a collection of diseases caused by uncontrolled cell growth and metastasis. The main treatment for cancer is chemotherapy, which generally kills fast growing cells nonspecifically and has many side effects. A different type of cancer treatment, called targeted therapy, aims to avoid general toxicity by using drugs that block the activity of specific gene products, usually encoded by oncogenes, which have been shown to drive tumor growth. To date, targeted therapies, alone or in combination with chemotherapies, have mainly been successful in rare subsets of patients with tumors addicted to single oncogenes. This has created a rationale to mainly treat patients with an oncogene-addiction (such as those carrying mutated or overexpressed kinases) with targeted therapies like erlotinib and trastuzumab, which inhibit human epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/ErbB2), respectively. Here, evidence is provided that targeted therapies are also effective in tumors that are dependent on multiple growth factors - a phenomenon that is called combinatorial ligand addiction. Specifically, it is shown that ligands that bind the EGFR family and the hepatocyte growth factor receptor (HGFR/MET) can activate protein kinase B (PKB/ AKT) across a broad set of cancer cell lines, suggesting that ligand signaling is redundant and widespread. It is also shown that ErbB ligands have distinct signaling dynamics and strengths, which provides a rationale for investigating each component of the ErbB signaling network. Using a systematic approach, we found that ErbB3 is an imp01tant therapeutic target even though it is not overexpressed and lacks kinase activity. Furthermore, it is shown that cell lines with and without known oncogene-addiction express autocrine ligands and have improved growth inhibition with drug combinations that include autocrine ligand-blocking antibodies. This research demonstrates that combinatorial ligand addiction creates a new rationale for therapeutic combinations to improve efficacy and prevent resistance in cancer cells that are treated with current targeted drugs. / 2999-01-01

Boston University. University Professors Program Senior theses. / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2999-01-02

Background: Psoriasis is a heterogeneous disease with several clinical manifestations; the symptoms are characterized by redness, scaliness and thickness of the skin. There are several treatment options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden. Methods: The Swedish Health Care Registers and the Swedish registry for systemic treatment of psoriasis PsoReg, were used to; estimate the incidence of psoriasis cases in the Swedish specialist care, to examine the treatment allocation and important factors related to the initiation of especially biologic treatment. Results: On average 9000 new psoriasis patients entered specialist care in Sweden each year under study, corresponding to an incidence of 98 patients per 100,000 person-years. In the treatment allocation analysis of the incident psoriasis cases in the Swedish specialist care Patients living in a Metropolitan Area and with a University degree were more likely to initiate a biologic treatment. By analysing biologic-naïve patients enrolled in PsoReg, PASI (the physician’s assessment of the psoriasis severity) and Psoriasis Arthropathy were shown to be two important factors associated with the initiation of biologic treatment while sex was not. Furthermore, it was also shown that the decision to initiate biological treatment was more strongly associated with PASI than with DLQI (the patients’ assessment of the disease impact Quality of Life). Conclusion: These studies indicate that there are inequalities in the assignments of systemic psoriasis treatments (especially in biologic treatment). Since the allocation of treatments should not depend on sex, education or residency in a Metropolitan Area but rather the need of care, it is important that future studies continue analysing possible factors that could influence the initiation of treatment in clinical practice.

No description available.

During the harvesting process, meat products can become contaminated with enteric pathogens, such as Escherichia coli O157:H7 and Salmonella Typhimurium. Surrogates for these pathogens would be beneficial for validating carcass decontamination treatments. Surrogate organisms are organisms that behave similarly to specific pathogens but are non-pathogenic and can be used to determine efficacy of decontamination regimes for pathogens. The surrogates proposed are non-pathogenic, ampicillin-resistant E. coli biotype I strains that were previously isolated from beef cattle hides. Each E. coli strain was transformed to express a fluorescent protein (red: EcRFP; green: EcGFP; yellow: EcYFP) that is detectable under an ultraviolet light source. Surface areas on hot boned beef carcasses (clod, brisket, outside round) were inoculated with a fecal slurry containing EcRFP, EcGFP, EcYFP and rifampicin-resistant E. coli O157:H7 and S. Typhimurium. Surface regions were then treated in a model spray cabinet using an initial water wash (28ºC) followed by treatments using 2% L-lactic acid (55ºC), hot water (95ºC at source) or a combination of the two. Treatments were compared for their effectiveness at reducing populations of inoculated (4.7 to 6.7 log CFU/cm2) E. coli, S. Typhimurium, EcRFP, EcGFP and EcYFP. Log reductions for inoculated organisms were calculated individually and then total and average surrogate cocktail values were calculated. All decontamination treatments reduced the inoculated numbers of pathogens and surrogates to near or below the detection limit of 0.5 log CFU/cm2. The combined treatment resulted in the greatest log reductions. The three individual surrogate organisms varied in log reductions according to the different decontamination treatments applied; however, log reductions for the total surrogate cocktail did not differ significantly from that of E. coli O157:H7. With the exception of EcYFP, the individual surrogates and average surrogate cocktail were significantly more resistant to microbial interventions including lactic acid than S. Typhimurium. Because abattoirs utilize different carcass decontamination treatments, it is difficult for one single fluorescent protein-producing isolate to accurately represent the behavior of E. coli O157:H7 or S. Typhimurium. Instead, surrogates should be used as a total cocktail to accurately represent the effectiveness of different treatments for reduction of enteric pathogens.

No description available.

Made available in DSpace on 2014-06-11T19:25:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-28Bitstream added on 2014-06-13T20:32:39Z : No. of bitstreams: 1 viana_ma_me_jabo.pdf: 561645 bytes, checksum: 0c2745a64509b4dad56b0591f7e32d50 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo do trabalho foi estudar a performance de Trichogramma exiguum e Trichogramma pretiosum, em ovos de populações de Plutella xylostella sob ação de a Bacillus thuringiensis. O experimento constou de quatro tratamentos por parasitoide, sendo: ovos da população suscetível (Ps) a Bt com mais de 100 gerações em laboratório (Testemunha); ovos da população submetida à pressão de seleção ao isolado HD-1 por mais de 40 gerações (Res); ovos da Ps pulverizados com HD-1 e ovos da Ps pulverizados com o isolado T08.024. As fêmeas foram individualizadas e alimentadas com uma gotícula de mel. Os testes realizados foram avaliados: a resposta funcional, capacidade de parasitismo, tabela de vida e teste de preferência. Para análise de resposta funcional foram testadas as densidades de 2, 4, 8, 16, 32 e 64 ovos, e a melhor densidade utilizada para os demais testes, utilizando as densidades de 32 e 8 para T. pretiosum e T. exiguum respectivamente. Os parâmetros avaliados foram: parasitismo, viabilidade, razão sexual, longevidade e período ovo-adulto. B. thuringiensis afeta os ovos de P. xylostella influenciando o parasitismo de Trichogramma sp., de maneira positiva ou negativa dependendo do isolado utilizado. A interação Trichogramma-Bt pode sofrer alterações de acordo com a espécie do parasitoide utilizada e do isolado de Bt, sendo necessário estudo das interações especificas antes de seu uso em conjunto / This research aimed the study of the performance of Trichogramma exiguum and Trichogramma pretiosum in eggs of Plutella xylostella populations under the action of Bacillus thuringiensis (Bt). The experiments consisted of four treatments for each parasitoid, as follows: eggs of the susceptible population (Ps) to Bt with more than 100 generations in the laboratory (Witness), eggs of the population subjected to selection pressure to isolate HD-1 for more than 40 generations (Res); Ps eggs sprayed with HD-1 and eggs of Ps sprayed with isolate T08.024. The females were individualized and fed with a drop of honey. Some parameters were evaluated: the functional response, parasitism capacity, life table and preference test. For analysis of functional response the densities of 2, 4, 8, 16, 32 and 64 eggs were tested, and the best densities were used for other tests, that were, 32 and 8 eggs for T. pretiosum and T. exiguum respectively. The parameters evaluated were: parasitism, viability, sex ratio, longevity and egg-adult period. Bacillus thuringiensis affected the eggs of Plutella xylostella influencing parasitism of Trichogramma sp., positively or negatively, depending on the isolate used. The interaction Trichogramma-Bacillus thuringiensis may change according to the species of parasitoid and the Bt strain used, it is necessary to study the specific interactions prior to use their two agents together

Orientador: Sérgio Antonio de Bortoli / Coorientador: Ricardo Antonio Polanczyk / Banca: Arlindo Leal Boiça Júnior / Banca: Fernando Hercos Valicente / Resumo: O objetivo do trabalho foi estudar a performance de Trichogramma exiguum e Trichogramma pretiosum, em ovos de populações de Plutella xylostella sob ação de a Bacillus thuringiensis. O experimento constou de quatro tratamentos por parasitoide, sendo: ovos da população suscetível (Ps) a Bt com mais de 100 gerações em laboratório (Testemunha); ovos da população submetida à pressão de seleção ao isolado HD-1 por mais de 40 gerações (Res); ovos da Ps pulverizados com HD-1 e ovos da Ps pulverizados com o isolado T08.024. As fêmeas foram individualizadas e alimentadas com uma gotícula de mel. Os testes realizados foram avaliados: a resposta funcional, capacidade de parasitismo, tabela de vida e teste de preferência. Para análise de resposta funcional foram testadas as densidades de 2, 4, 8, 16, 32 e 64 ovos, e a melhor densidade utilizada para os demais testes, utilizando as densidades de 32 e 8 para T. pretiosum e T. exiguum respectivamente. Os parâmetros avaliados foram: parasitismo, viabilidade, razão sexual, longevidade e período ovo-adulto. B. thuringiensis afeta os ovos de P. xylostella influenciando o parasitismo de Trichogramma sp., de maneira positiva ou negativa dependendo do isolado utilizado. A interação Trichogramma-Bt pode sofrer alterações de acordo com a espécie do parasitoide utilizada e do isolado de Bt, sendo necessário estudo das interações especificas antes de seu uso em conjunto / Abstract: This research aimed the study of the performance of Trichogramma exiguum and Trichogramma pretiosum in eggs of Plutella xylostella populations under the action of Bacillus thuringiensis (Bt). The experiments consisted of four treatments for each parasitoid, as follows: eggs of the susceptible population (Ps) to Bt with more than 100 generations in the laboratory (Witness), eggs of the population subjected to selection pressure to isolate HD-1 for more than 40 generations (Res); Ps eggs sprayed with HD-1 and eggs of Ps sprayed with isolate T08.024. The females were individualized and fed with a drop of honey. Some parameters were evaluated: the functional response, parasitism capacity, life table and preference test. For analysis of functional response the densities of 2, 4, 8, 16, 32 and 64 eggs were tested, and the best densities were used for other tests, that were, 32 and 8 eggs for T. pretiosum and T. exiguum respectively. The parameters evaluated were: parasitism, viability, sex ratio, longevity and egg-adult period. Bacillus thuringiensis affected the eggs of Plutella xylostella influencing parasitism of Trichogramma sp., positively or negatively, depending on the isolate used. The interaction Trichogramma-Bacillus thuringiensis may change according to the species of parasitoid and the Bt strain used, it is necessary to study the specific interactions prior to use their two agents together / Mestre

The foundation of the Jaburu I dam it is a classical performance case of foundations in sandstone sedimentary rock. The continuous monitoring of the dam has been the detected the non-regular seepages and adopted in establishing the planning and execution of the remediation campaigns in way to keep the foundation and damâs structures in safety conditions over three decades of operation, in despite of the ineffectiveness of conventional treatment foundation in sedimentary formation that had been used. Seepage anomalies indentified since the first filling of the reservoir in some regions of embankment and its foundation, detaching a significant flow in the left abutment which reached the maxima discharge of 47 l / s in 1988. Since then new points of resurgences have been identified and monitored by flow gages located in the downstream region. This monograph presents the events recorded in the flow gages and the remedial campaigns adopted to reduce the seepage in the foundation, embankment and abutments of the dam, as well as others specific interventions designed to recover the internal drain, stabilize the dam and to fill the cavities formed by the decomposition of the sandstone rock in the foundation. After the publication of the Law 12.334/2010, which established the National Policy of Dam Safety, it was established a complete list of responsibilities related to the safety of dams in Brazil, some of them already taken as routine by the Government of Cearà since 2002. This monograph recommends to the rock foundations of the dam, treatments with new sealing technologies that would mitigate the present anomalies. / A fundaÃÃo da Barragem Jaburu I apresenta comportamento clÃssico em se tratando de fundaÃÃes em rocha sedimentar tipo arenÃtico. O monitoramento contÃnuo deste empreendimento tem sido o principal indicador no estabelecimento do planejamento e execuÃÃo das aÃÃes de tratamento das fundaÃÃes e recuperaÃÃo das estruturas comprometidas no decorrer de trÃs dÃcadas, onde se pode verificar a pouca eficÃcia do tratamento convencional de fundaÃÃo em ambiente sedimentar. Desde o primeiro enchimento do reservatÃrio foram identificadas anomalias no maciÃo de terra e na fundaÃÃo, em forma de percolaÃÃo, juntando-se a estas uma significativa vazÃo na ombreira esquerda que alcanÃou um pico de 47 l/s, em 1988. Desde esta ocasiÃo, novos pontos de surgÃncias foram identificados e monitorados por meio de medidores de vazÃo na regiÃo de jusante. Apresentase, assim, os acontecimentos registrados na barragem e os programas de tratamentos adotados para reduzir as percolaÃÃes pela fundaÃÃo, do corpo da barragem e ombreiras, assim como outras intervenÃÃes realizadas com o propÃsito de drenar o fluxo, estabilizar a barragem e obturar as cavidades provenientes da decomposiÃÃo da rocha arenÃtica. Com o advento da Lei 12.334/2010, que instituiu a PolÃtica Nacional de SeguranÃa de Barragens, foi estabelecida uma cadeia completa de responsabilidades relacionadas à seguranÃa das barragens construÃdas no Brasil, sendo que algumas das aÃÃes propostas jà sÃo adotadas pelo Governo do CearÃ, desde 2002. Esta dissertaÃÃo conclui recomendando aÃÃes de reabilitaÃÃo da rocha de fundaÃÃo da barragem, com novas tecnologias de impermeabilizaÃÃo, de forma a mitigar as anomalias.